Fig 1.
Schematic representation of the hybrid model.
The hybrid model consists of a vector-based Boolean module of nutrient signaling and an enzyme constrained module of the central carbon metabolism. The Boolean module is a dynamic module including Snf1, PKA, and TORC1 pathway as well as crosstalk between them. The dynamic module reaches a steady-state and the activity of the transcription factors acts as input in a regulatory network constraining the enzyme constraint model of the central carbon metabolism. The solution is used to determine the activity of the Boolean input.
Fig 2.
The Boolean module is a dynamic module including Snf1, PKA, and TOR pathway as well as crosstalk between them.
Crosstalk events between the pathways are depicted in grey. Unknown mechanisms are represented by dashed lines.
Fig 3.
(A) Absolute log10-transformed ratio between predicted and measured protein abundance values in respiration and fermentation for the purely enzyme-constrained and hybrid models. (B) Evaluation of isoenzymes utilization predictions, comparing the ecModel and hybrid model on respiratory and fermentative conditions against experimental data on protein expression (absence/presence). FMI—Fowlkes-Mallows index. (C) Comparison of individual isoenzymes utilization between models’ predictions and experimental data. Color indicates presence or absence of a given protein in the predictions of the ecModel, hybrid model and experimental data on protein expression.
Fig 4.
The core reactions in the metabolism under (A) respiration and (B) fermentation are shown. The fluxes are represented by the width of the connectors where dotted lines represent zero flux. The color of the connectors represents the change in flux from the unregulated ecModel compared to the regulated hybrid model. The FCCs are represented in the figure where the unregulated case is depicted by circles and compared to the regulated case depicted in squares.
Table 1.
Size metrics for the Boolean, original metabolic model, and its enzyme-constrained version.